An Association Between FNDC5, PGC-1 alpha Genetic Variants and Obesity in Chinese Children: A Case- Control

Background: Fibronectin type III domain containing protein 5 (FNDC5) gene encodes irisin that regulates adipose tissue metabolism. Peroxide-proliferator-activated receptor gamma coactivator 1 alpha (PGC-1 alpha) is a powerful promoter of mitochondrial biosynthesis and oxidative metabolism, which plays an important role in inducing heat production and energy consumption of brown fat. PGC1-alpha expression stimulated an increase in expression of FNDC5.Purpose: The aims of this study were to analyze the association between FNDC5, PGC-1 alpha genetic variants and overweight or obesity in Chinese children and adolescents.Methods: A total of 198 children and adolescents with overweight or obesity and 198 children and adolescents with normal weight were screened according to gender and age 1:1. The healthy eating behaviors, moderate-to-vigorous physical activity time were surveyed using food frequency questionnaire and CLASS questionnaire, respectively. Genotypes of FNDC5 and PGC-1 alpha gene were detected using SNaPshot method.Results: GT genotype of FNDC5 (rs16835198) increased the risk of overweight or obesity in boys (OR (95% CI): 1.68 (1.00, 2.93)) based on overdominant model; GG genotype of FNDC5 (rs16835198) decreased the risk of overweight or obesity in girls and boys (OR (95% CI): 0.45 (0.21,0.97), 0.45 (0.24, 0.83), respectively) based on dominant model; TT genotype of FNDC5 (rs16835198) increased the risk of overweight or obesity in girls based on recessive model (OR (95% CI): 2.46 (1.19, 5.05)), and based on the additive model (OR (95% CI): 3.82 (1.49, 9.80)). There was significant interaction between FNDC5 (rs16835198) and PGC-1 alpha (rs3755863, rs8192678), healthy eating behaviors, moderate-to-vigorous physical activity time, interaction between PGC-1 alpha (rs8192678) and moderate-to-vigorous physical activity time in the occurrence of overweight or obesity in Chinese children and adolescents.Conclusion: FNDC5 (rs16835198) played an independent or interactive role with PGC-1 alpha (rs3755863, rs8192678), healthy eating behaviors, moderate-to-vigorous physical activity time in the occurrence of overweight or obesity in Chinese children and adolescents.